The ability of the CNS to regulate peripheral haemodynamics is obviously insufficient to maintain arterial pressure within normal levels in hypertensive states. Moreover it is becoming increasingly evident that the CNS in fact contributes to the development and maintenance of the hypertension either because of genetic abnormalities (spontaneously hypertensive rats) or because it receives abnormal signals from the periphery (reset baroreceptors, excessive renal afferent inputs, excessive angiotensin levels etc.) which reflexly trigger inappropriate hormonal or sympathetic responses. The point of the present proposal is to focus on three regulatory mechanisms and to investigate their alterations in several hypertensive models in the rat. The first project consists in comparing the haemodynamic characteristics and sympathetic activity of two angiotensin II-dependent hypertensive models (2 KIC rats and rats rendered hypertensive via low dose infusion of angiotensin-II). Its main purpose will be to determine the specific contribution of A-II in renal hypertension. The second part consists in a neurophysiological investigation of the cardiovascular integration which takes place in the anterior ventrolateral medulla at the level of identified medullospinal sympathetic efferents. This study will be performed in SHR's, renal hypertensive animals (2 KIC rats) and animals rendered hypertensive by continuous infusions of A-II. Its object will be to determine directly the potential contribution of identified central sympatho-motor neurons to the hypertension. The third project consists in studying with molecular biological approaches the role of the central renin-angiotensin system. The presence of mRNA coding for angiotensin-II containing peptides and the exact nature of these molecules will be investigated. The regional distribution of this synthetic ability and its potential alteration in hypertension will be studied in several animal models including SHR's and AII-dependent hypertensive models (2 KIC rats and animals rendered hypertensive by infusion by low A-II doses). These three projects are presented as a single package because their completion requires a pool of techniques unavailable to any given contributing laboratory separately.